1. Field of the Invention
This invention relates to the field of capillary electrophoresis. More particularly, this invention relates to capillary electrophoresis devices having optical waveguides that direct excitation radiation to the electrophoresis channels.
2. Description of Related Art
Capillary electrophoresis is an established technique for separating chemical components. A sample solution containing the chemical components to be separated is placed in an electrophoresis channel containing an electrophoretic medium. For example, the electrophoresis channel may be provided by a length of capillary tubing. Upon the application of an electric field along the length of the electrophoresis channel, the different chemical components within the sample migrate at distinct rates towards the oppositely charged end of the capillary, the rate of migration being dependent on the chemical substance""s electrophoretic mobility in the electrophoretic medium. As a result of their distinct rates of migration, the various chemical components become separated as they progress along the electrophoresis channel and, thus, can be separately detected.
Various means for detecting the separated chemical components are known. If the chemical components of interest are fluorescent, then they can be conveniently detected by inducing their fluorescence. In particular, many biological components, such as proteins and nucleic acids, even if not themselves fluorescent, can be made fluorescent by conjugating them to any number of fluorophores using well-known techniques. In the induced fluorescence approach, electromagnetic radiation at an excitation wavelength, the wavelength needed to induce fluorescence, is directed to a particular point in the electrophoresis channel. The excitation wavelength is typically in the ultra-violet or visible spectrum, and the source of the excitation radiation is typically a laser. The induced fluorescence radiation may then be detected by a light-sensitive detector, such as a charge-coupled device (CCD),photodiode array, or photomultiplier tube (PMT).
The analytical capacity of capillary electrophoresis techniques is often multiplied by using many electrophoresis channels in parallel. Typically, these multiple electrophoresis channels are arranged in the same plane with their start and finish points aligned. Directing the excitation radiation to each of the electrophoresis channels is more complicated in this geometry, especially since, to allow for parallel detection, it is preferable to apply the excitation radiation to each electrophoresis channel at the same distance from the starting point at the same time.
In one approach that has been used with an array of electrophoresis capillaries, a beam expander and a cylindrical lens are used to focus laser light into a thin line that intersects the axes of the capillaries. A significant disadvantage with this approach, however, is that much of the excitation radiation will be wasted because it will fall between the cores of the capillaries, which is where the components to be detected are located. Moreover, the distribution of intensity along the focussed line will be highly non-uniform, unless the focussed line is much longer than the width of the capillary array, thereby causing even more of the excitation radiation to be wasted.
Optical waveguide systems have also been used to direct the excitation radiation to multiple electrophoresis capillaries. For example, in the systems disclosed in U.S. Pat. Nos. 5,312,535; 5,324,401; and 5,413,686, each electrophoresis capillary is provided with at least one optical fiber that directs the excitation radiation to it. However, such systems become bulky and complex as the number of electrophoresis capillaries becomes large. Moreover, each optical fiber must be carefully aligned with each capillary in order to achieve efficient and uniform illumination of each capillary.
U.S. Pat. No. 5,790,727 discloses a system wherein the capillaries are arranged in a parallel array so that the capillaries themselves act as optical waveguides. In particular, refraction at the cylindrical surfaces of the capillaries confine excitation radiation applied from the side of the array to the core of each capillary in the array. While potentially efficient, this approach requires particularly precise arrangement of the capillaries so that they will form waveguides.
Increasingly, capillary electrophoresis is conducted in microfluidic devices. Instead of using individual capillaries, the electrophoresis channels are provided as microfluidic channels formed into a substrate, such as glass, silicon, or plastic. To allow detection by induced fluorescence, the microfluidic device may include an optically transparent portion so that the excitation radiation can reach the electrophoresis channels. An example is the microfluidic device disclosed in U.S. Pat. No. 5,958,694. However,this device included only a single capillary electrophoresis channel. When microfluidic electrophoresis devices include multiple electrophoresis channels, a similar difficulty in illuminating the multiple channels with the excitation radiation arises, as when discrete capillaries are used.
The present invention provides a capillary electrophoresis device comprising a substrate and an optical waveguide system. A plurality of electrophoresis channels are formed in the substrate. The optical waveguide system has a source port and a plurality of output port and transmits light entering the source port into each one of the electrophoresis channels through one of the output ports.